The association of Congenital Heart Defects & Down Syndrome
August 18, 2020 | Contributed by Dr Mani Ram Krishna
Down Syndrome (or Down’s Syndrome), was first described in great detail by John Langdon Down in the 19th century. It is the commonest genetic condition in mankind with an estimated incidence of 1 in 1000 live births. The condition is caused by the presence of a third copy of chromosome 21 (There are normally only 2 copies of each chromosome in our cells). Indeed because of the stigmata associated with Down syndrome, some medica
l authorities prefer to call this condition Trisomy 21 (T21). The condition is characterized by distinct facial features – slanted eyes, flat nose and small chin, an appearance often referred to as “Mongoloid faces”. The facial appearance is similar irrespective of the ethnicity of the individual and was the feature that drew the attention of Langdon Down towards this condition.
The diagnosis of T21 is usually readily apparent after birth because of the characteristic clinical appearance. Given the fact that it is the commonest genetic condition as well as the commonest cause of subnormal mental development, a lot of effort has been expended on identifying this condition during pregnancy. It has been observed that the incidence of pregnancies with T21 increases with increasing maternal age with a very high proportion in women above 37 years of age. The condition also results in hormonal abnormalities in the mother which can be measured in a blood sample as well as sonological abnormalities in the early fetal period (an increased collection of fluid behind the neck of the fetus referred to as nuchal translucency which can be detected by means of an ultrasound examination during the first trimester of pregnancy between 11-14 weeks). The combination of maternal age, blood parameters and ultrasound evaluation are used as a screening test to determine the risk of T21 in the fetus. If this is deemed high risk, the diagnosis will need to be confirmed by performing a genetic test on the cells of the fetus which is usually obtained by collecting fluid present around the baby in the womb and looking at fetal cells in the fluid.
Approximately half of children with T21 have a major congenital heart disease (CHD) (the reported incidence varies between 40-63%). In comparison, the incidence of CHD in the general population is 0.8%. The exact genetic reason for the increased association with CHD is not clearly known although a number of genes present in chromosome 21 have been implicated. Most of the recent research has focused on genes involved in attachment between the various cells of the heart with a gene called CRELD1 believed to be an important candidate gene. CHD treatment in India is still a subject of awareness among the masses, especially considering children with T21.
A variety of CHD have been known to occur in T21. Approximately 30-40% of children with T21 have a CHD called Atrio-Ventricular Septal Defect (AVSD). This condition is characterized by holes between the top 2 chambers of the heart (Atrial Septal Defect) as well as the bottom 2 chambers of the heart (Ventricular Septal Defect). In addition, a single valve guards the junction between the top and bottom chambers in contrast to 2 valves (one on the right side and one on the left side) in normal children. The association of AVSD with T21 is so strong that detection of AVSD in a fetus should prompt testing for T21. The other CHD commonly found in T21 in decreasing frequency of incidence include ventricular septal defect, atrial septal defect and Tetralogy of Fallot (ToF).
The clinical presentation of CHD in T21 is similar to those in other infants with frequent respiratory infections, poor weight gain and bluish discoloration. However a minority of children may remain asymptomatic despite the presence of CHD. The surgical management of these conditions is the same as that in children without the genetic condition. Children with T21 are however at a slightly higher risk of postoperative complications which include requiring artificial respiratory support for a longer duration, a longer stay in the intensive care unit and a small increase in the risk of death during surgery. This is usually attributed to the poor muscle tone in these children.
Children who have large holes in the heart such as VSD and AVSD should be operated before 2 years of age. If they are not operated in a timely fashion, the condition could result in either death due to respiratory infections or an irreversible increase in the lung pressure (pulmonary arterial hypertension). When irreversible damage sets in, surgical correction can no longer be performed, and children are deemed inoperable. Such irreversible damage occurs earlier in children with T21 and typically occurs at around 1 year of age. Hence early detection becomes paramount in the management of CHD in T21. With advanced technology, CHD treatment in India has improved greatly in Tier 1 cities across the country.
CHD is also the most important contributor to mortality and morbidity associated with T21 in early childhood. Hence when T21 is diagnosed clinically, an infant should undergo evaluation for CHD through referral to a pediatric cardiologist for an echocardiogram irrespective of the presence of clinical features of CHD.